Progress in TB treatment
The non-profit Global Alliance for TB Drug Development provides its latest updates on TB drug research.
The non-profit Global Alliance for TB Drug Development provides its latest updates on TB drug research.
TUBERCULOSIS (TB) is the world’s deadliest infectious disease, and a top 10 cause of death worldwide.
In its 2016 World TB Report, the World Health Organization (WHO) estimated that 10.4 million people became sick with TB. Of these, 580,000 cases were drug-resistant.
Almost two million people die from TB each year.
TB preys on the vulnerable. Women, children, and people with HIV/AIDS are among those most at risk of this disease, which is transmitted through the air and thrives in weakened immune systems.
TB also propagates a cycle of poverty among those who can least afford it; more than 95% of TB deaths take place in low- and middle-income countries.
The high costs of treatment, especially for drug-resistant TB, place an extreme burden on health systems, in addition to that on patients and their families.
In September 2016, the United Nations General Assembly held its first-ever Highlevel Meeting on Antimicrobial Resistance (AMR).
AMR, the result of microorganisms no longer responding to commonly used antibiotics, has emerged as one of the defining global health issues of our time.
Drug-resistant TB can easily develop in patients when medicine is not properly taken or administered.
It can be spread through the air, just like drug-sensitive TB, and is extremely difficult to cure.
Estimates from the AMR Review, a report commissioned by the British government, indicate that almost 30% of deaths related to AMR are caused by drug-resistant TB.
Today’s prevailing TB drugs, developed half a century ago, aren’t working the way they need to.
For those with the more common form of “drug sensitive” TB, the shortest available treatment – a best case scenario – consists of daily pills for six months.
For those with multiple forms of drugresistant TB, the following is the treatment reality: nine months to two years of a dozen or more pills per day, along with six months of daily injections.
And for those unfortunate enough to have extensively resistant TB, even if they take every one of those 20,000 toxic pills and hundreds of injections, they will still have less than a one-in-three chance of survival.
In some studies, that number is as low as 16%.
In order to bring the TB epidemic to an end, patients will need better options than these long, toxic and expensive regimens.
New combinations
In 2016, the non-profit Global Alliance for TB Drug Development (TB Alliance) realised significant progress in advancing new drug regimens that could significantly impact the TB pandemic.
Results from the NC-005 trial and interim results from the Nix-TB trial point to the possibility of a new treatment paradigm where countries could use just two short, simple regimens to treat all people with TB, no matter their resistance profile.
These regimens share two powerful new drugs, bedaquiline (B) and pretomanid (Pa), which the TB Alliance began studying in combination in 2012.
When bedaquiline and pretomanid are paired with moxifloxacin (M) and pyrazinamide (Z) (BPaMZ), results show that the regimen has promise to be a common therapy for virtually all patients with either drug-sensitive TB and or multi-drug resistant TB (MDR-TB) – the vast majority of TB patients.
More than three-fourths of patients taking BPaMZ were clear of TB bacteria after this initial two-month treatment (a range of 78%96% depending on whether their TB was fully sensitive to three or all four drugs in the regimen), compared with just 51% taking the standard first-line treatment.
If successful in future trials, the BPaMZ regimen could help rationalise and unify TB treatment by offering countries a single, four to six month, injection-free regimen that could treat the vast majority (estimated at approximately 99%) of patients.
Meanwhile, early data from the Nix-TB trial shows that when bedaquiline and pretomanid are paired with linezolid (L) (BPaL), it creates the potential to treat the most deadly and difficult-to-treat TB, extremely drug resistant TB (XDR-TB), in just six months with a dramatically simpler, safer and more effective regimen.
Building on the promising interim results of the BPaL regimen, the TB Alliance aims to launch the ZeNix trial later this year in South Africa, Georgia, Belarus and Russia.
This clinical trial will seek to optimise the use of linezolid in the regimen, including determining the best dose and treatment duration needed to ensure safe, effective treatment, while minimising side-effects.
At the same time, the TB Alliance is planning for the development of a patient access programme for the BPaL regimen, working with partners to develop a framework in which patients with urgent medical needs are able to access this ground-breaking treatment prior to regulatory approval.
If funding can be secured, TB Alliance will be the first product development partnership to offer such a programme.
These two regimens have the potential to transform the treatment landscape.
Both BPaMZ and BPaL can be maximally implemented with existing diagnostics, and countries might only need to stock a few oral drugs to treat all types of TB in treatment regimens of four to six months.
That would be a major improvement from today, where countries devise regimens from more than 20 drugs and injections, which then must be taken for six to 24 months or longer, and in drug-resistant TB, produce poor – if not dire – outcomes.
Results from the NC-005 and Nix-TB trials were presented at the 47th Union World Conference on Lung Health and at the 2017 Conference on Retroviruses and Opportunistic Infections.
Kid-friendly meds
Each year, one million children get sick with TB and 210,000 die from it – that’s nearly 575 children dying each and every day.
Last year, TB Alliance and its partners made huge progress in the introduction of the first appropriately dosed child-friendly TB medicines.
Around the world, most children don’t have access to TB medicines in the proper doses or formulations.
Care providers and parents have to crush or chop adult pills to approximate the correct dose for children.
This is a daily struggle – for six long months – and creates a guessing game of whether children receive the right dose.
Ultimately, these medicines can negatively impact adherence, outcomes and fuel the development of drug-resistant TB.
Improved medicines for children with drug-sensitive TB means tablets in the correct fixed dose combinations of the three most commonly used anti-TB drugs – rifampicin, isoniazid and pyrazinamide – used for the initial two months of treatment, followed by four months of rifampicin and isoniazid.
These products offer significant advantages over previous drugs including:
● Fixed dose combinations in the correct, WHO-recommended dose – no need for crushing or chopping
● Quickly dispersible in liquid – easy for parents to give and for children of all ages to take
● Palatable fruit flavours
In just one year, more than 325,900 treatment courses of these new medicines had been ordered – enough to meet the needs of 90% of the children reported every year to national programs.
Today, 36 countries have ordered the improved medicines, with many more expected in the years ahead.
The rapid introduction of these improved childhood TB medicines may be the most successful TB product launch in history.
The new childhood TB medicines also achieved the TB Alliance patient access commitment, known as the AAA Mandate.
These new medicines are easily adoptable as they are endorsed by WHO treatment guidelines, widely available in the public and private sector, and affordable.
As countries continue to roll out these products, children around the world stand to benefit from dramatically improved TB treatments. – Adapted from the TB Alliance 2016 Annual Report